Circos on the Cover Of Journal of Pathology

The June 2013 issue of the Journal of Pathology features a pair of Circos plots on the cover, based on the Weier et al. article describing TMPRSS2 and ERG rearrangements in prostate cancer.

"TMPRSS2–ERG rearrangements occur in approximately 50% of prostate cancers and therefore represent one of the most frequently observed structural rearrangements in all cancers."

Weier C, Haffner MC, Mosbruger T et al. 2013 Nucleotide resolution analysis of TMPRSS2 and ERG rearrangements in prostate cancer J Pathol 230:174-183.

Circos on the Cover Of Nature's Asian Journal of Andrology

The May 2013 Special Issue of Asian Journal of Andrology presents the outcomes from the Sixth Annual Forum on Prostate Disease (6th FPD), which was held on June 8-9, 2012 in Shanghai, China [source: nature.com]. The cover art for the issue shows a Circos plot of 90 significantly recurrent molecular alterations in prostate cancer from an analysis of 372 prostate tumors discussed in the Wyatt et al. review article.

The review summarizes the current state of understanding of prostate cancer, "including the sentinel role of copy number variation, the growing spectrum of oncogenic fusion genes, the potential influence of chromothripsis, and breakthroughs in defining mutation-associated subtypes. Increasing evidence suggests that genomic lesions frequently converge on specific cellular functions and signalling pathways, yet recurrent gene aberration appears rare".

Wyatt AW, Mo F, Wang Y et al. 2013 The diverse heterogeneity of molecular alterations in prostate cancer identified through next-generation sequencing Asian J Androl 15:301-308.

Brain Volume in Epilepsy

Pardoe et al. find that "Sodium valproate use in epilepsy is associated with parietal lobe thinning, reduced total brain volume, and reduced white matter volume."

The cover image shows antiepileptic drug combinations in intractable focal epilepsy cases. Linked drugs were being taken concurrently by an individual. Valproate cases are highlighted in orange.

Pardoe, HR, Berg, AT, and Jackson, GD 2013Sodium valproate use is associated with reduced parietal lobe thickness and brain volume Neurology 80(20):1895-1900.

Improving miR-mRNA Predictions

Rijlaarsdam et al. describe an algorithm for improving miR-mRNA predictions.

"Algorithms predicting miR-mRNA interactions generate high numbers of possible interactions, many of which might be non-existent or irrelevant in a certain biological context. It is desirable to develop a transparent, user-friendly, unbiased tool to enrich miR-mRNA predictions."

Rijlaarsdam MA, Rijlaarsdam DJ, Gillis AJ et al. 2013 miMsg: a target enrichment algorithm for predicted miR-mRNA interactions based on relative ranking of matched expression data Bioinformatics

Round is peachy

The International Peach Genome Initative has ensured that peach, a diploid Prunus species, is one of the best genetically characterized deciduous trees.

"Rosaceae is the most important fruit-producing clade, and its key commercially relevant genera (Fragaria, Rosa, Rubus and Prunus) show broadly diverse growth habits, fruit types and compact diploid genomes."

No mention of fuzz is made.

Verde I, Abbott AG, Scalabrin S et al. 2013 The high-quality draft genome of peach (Prunus persica) identifies unique patterns of genetic diversity, domestication and genome evolution Nat Genet

Circos in Wired's Best Scientific Figures of 2012

Wired's Best Scientific Figures of 2012 includes an image created with Circos.

"Though it's long been assumed that each cell in a body contains the same basic genomic blueprint, research now suggests that genomes actually vary between cells in the same body. The figure comes from a study of copy number variation, in which stretches of DNA are repeated multiple times. In all 23 chromosomes (arrayed in radial form) researchers found copy number differences unique to each cell's physical origin (color coding). Brain cells, for example, had quite different genomes from lung cells."

O'Huallachain M, Karczewski KJ, Weissman SM et al. 2012 Extensive genetic variation in somatic human tissues Proc Natl Acad Sci U S A 109:18018-18023.

Circos swims with fish

Howe et al. report on the zebrafish reference genome.

"Zebrafish have become a popular organism for the study of vertebrate gene function. The virtually transparent embryos of this species, and the ability to accelerate genetic studies by gene knockdown or overexpression, have led to the widespread use of zebrafish in the detailed investigation of vertebrate gene function and increasingly, the study of human genetic disease."

Howe K, Clark MD, Torroja CF et al. 2013 The zebrafish reference genome sequence and its relationship to the human genome Nature

Circos, Lung Cancer and Smoking

Imielinski et al. visualize mutations in the exome and genome sequences of 183 lung adenocarcinomas to reveal recurrent somatic mutations in the splicing factor gene U2AF1 and RBM10 and ARID1A, as well as EGFR and SIK2. Grouping the data revealed clusters that correlated with smoking history.

Imielinski M, Berger AH, Hammerman PS et al. 2012 Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing Cell 150:1107-1120.

Circos and Hive Plots describe regulatory networks

One of the first uses of Circos in the literature was to visualize the grapevine genome. Since then, Circos has gained popularity in the plant literature and has been used to look at poplar, rice and wheat, prairie cord grass, Arabidopsis as well as peach, apple and strawberry.

Here, Cockram et al. describe and visualize the control exerted by genes on the flowering time of members in the true grasses family (Poaceae).

Cockram J, Thiel T, Steuernagel B et al. 2012 Genome Dynamics Explain the Evolution of Flowering Time CCT Domain Gene Families in the Poaceae PLoS One 7:e45307.

Towards a Human Pan-Genome

As reported in Wired, Li et al. use Circos to visualize the comparison of structural variation in two sequenced human genomes: Asian and Yoruban (African). It's been over 10 years since the first reference genome (comprising DNA from multiple individuals) was reported. Technological advancements have made it possible to now sequence 1000's of human genomes to identify genetic variations for tracing evolution, determining population patterns, and assessing disease susceptibility and other phenotypic traits.

Li Y, Zheng H, Luo R et al. 2011 Structural variation in two human genomes mapped at single-nucleotide resolution by whole genome de novo assembly Nature biotechnology 29:723-730.

Li R, Li Y, Zheng H et al. 2010 Building the sequence map of the human pan-genome Nature biotechnology 28:57-63.

Hemolytic–Uremic Syndrome Outbreak

Rasko et al. use Circos to show how the E. coli strain implicated in the German outbreak of hemolytic-uremic syndrome varies from other strains in their New England Journal of Medicine paper, where they find that "the genome of the German outbreak strain can be distinguished from those of other O104:H4 strains because it contains a prophage encoding Shiga toxin 2 and a distinct set of additional virulence and antibiotic-resistance factors."

NEJM created an animation that explains the visualizations. The paper was blogged by Pacific Biosciences.

Rasko DA, Webster DR, Sahl JW et al. 2011 Origins of the E. coli Strain Causing an Outbreak of Hemolytic-Uremic Syndrome in Germany The New England journal of medicine published ahead of print:-.

Circos in Simon Fraser University's AQ magazine (Apr 2011)

A Circos image appears as part of a spread in SFU's biannual AQ Magazine. The composite accompanies my photos of our laboratory and computer equipment.

The image was adapted from Figure 1 of our paper "Evolution of an adenocarcinoma in response to selection by targeted kinase inhibitors".

Jones SJ, Laskin J, Li YY et al. 2010 Evolution of an adenocarcinoma in response to selection by targeted kinase inhibitors Genome Biol 11:R82.

Circos Maps Cancer Landscapes

Nature features an article by Heidi Ledford, The Cancer Genome Challenge, which discusses the progress and challenges of identifying structural variation signatures in cancer genomes.

Circos images are used throughout the piece, taken from the COSMIC project (Catalogue of Somatic Mutations in Cancer).

Ledford H 2010 Big science: The cancer genome challenge Nature 464 (7291) 972-974.

Massive Genomic Rearrangement Acquired in a Single Catastrophic Event during Cancer Development

Stephens et al. report on a phenomenon by which a cell accumulates a large number of rearrangements in a single catastrophic event. This phenomenon, which they call chromothripsis, can be seen in at least 2%–3% of all cancers and in about 25% of bone cancers.

1Stephens PJ, Greenman CD, Fu B et al. 2011 Massive Genomic Rearrangement Acquired in a Single Catastrophic Event during Cancer Development Cell 144:27-40.

Little Fly, Thy Summer's Play...

In a collaboration with Derek Baccus from Pearson Science, Martin Krzywinski designed the cover illustration for the 3rd edition of iGenetics by Peter Russell.

The cover image shows a comparison of human and fruit fly genomes. The links indicate orthologous genes — genes in both genomes whose proteins are similar.

This cover won the cover award at 39th Annual 2009 Bookbuilders West Book Show.

Successive Duplications in Paramecium

A visual representation of ancestry analysis of 85 dog breeds and Eurasian gray wolves.

17Vonholdt BM, Pollinger JP, Lohmueller KE et al. 2010 Genome-wide SNP and haplotype analyses reveal a rich history underlying dog domestication Nature 464 (7290) 898-902.

Successive Duplications in Paramecium

This unusual, but effective, Circos image shows successive duplications in the Paramecium genome.

The exterior circle displays all chromosome-sized scaffolds, and the three interior circles show the reconstructed sequences obtained by fusion of the paired sequences from each previous step.

57Aury JM, Jaillon O, Duret L et al. 2006 Global trends of whole-genome duplications revealed by the ciliate Paramecium tetraurelia Nature 444 (7116) 171-178.

Circos Illustrates Genome Structure of Maize

The Maize sequence paper uses Circos to show genome structure and annotations. Links inside the circle show homologous sites of duplicated gene blocks.

40Schnable PS Ware D Fulton RS et al. 2009 The B73 maize genome: complexity, diversity, and dynamics Science 326 (5956) 1112-1115

Circos Introduced in the New York Times

My first Circos infographic to be published in the New York Times introduces the idea of sequence similarity curves linking circularly composed ideograms.

Working with David Constantine, I illustrated the similarity between chromosome 1 of mouse, rhesus, chimp, and chicken to that of human.

One of the smaller panels in the infographic was subsequently used by the Alliance of Lupus Research in their Faces of Lupus II video.